Stimulation of endothelial adenosine Al receptors enhances adhesion of neutrophils in the intact guinea pig coronary system

Objective: The primary aim was to determine the action of pathophysiologically relevant adenosine concentrations (0.1-1 μM) on adhesion of neutrophils to coronary endothelium. Further aims were to evaluate the nature and localisation of the adenosine receptor involved. and to assess the effect of endogenous adenosine. Methods: Adhesion was studied in isolated perfused guinea pig hearts by determining the number of cells emerging in the coronary effluent after intracoronary bolus injections of 600 000 neutrophils prepared from guinea pig or human blood. The system was characterised by the use of the proadhesive stimulus thrombin. Results: A 5 rnin infusion of adenosine (0.1-0.3 μM) or the A1 receptor agonist N6-cyclopentyladenosine (CPA, 0.01 μM) significantly increased adhesion from about 20% (control) to 30%. This effect was prevented by the A1 receptor antagonist dipropyl-8-cyclopentylxanthine (DPCPX. 0.1 μM). It was not diminished by cessation of adenosine infusion 90 s prior to neutrophil injection. At a higher concentration of adenosine (1 μM), adhesion did not seem to be enhanced. However, coinfusion of the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX. 0.1 μM) with 1 μM adenosine unmasked the A1 action, adhesion rising to 39%. Adenosine had a quantitatively identical effect on adhesion of human neutrophils. Total ischaemia of 15 min duration raised adhesion of subsequently applied neutrophils to 35%. This effect was completely blocked by DPCPX, as well as by ischaemic preconditioning (3 X 3 min). Preconditioning raised initial postischaemic coronary effluent adenosine from about 0.8 μM to 1.5 μM. Conclusions: The findings suggest a bimodal participation of adenosine in the development of postischaemic dysfunction by an endothelium dependent modulation of neutrophil adhesion. Stimulation occurs via endothelial A1 receptors at submicromolar adenosine levels, whereas cardioprotection by adenosine may in part relate to the use of pharmacologically high concentrations of adenosine or enhanced endogenous production after preconditioning

Paired accelerated arames: The perfect interferometer with everywhere smooth wave amplitudes

Rindler's acceleration-induced partitioning of spacetime leads to a nature-given interferometer. It accomodates quantum mechanical and wave mechanical processes in spacetime which in (Euclidean) optics correspond to wave processes in a ``Mach-Zehnder'' interferometer: amplitude splitting, reflection, and interference. These processes are described in terms of amplitudes which behave smoothly across the event horizons of all four Rindler sectors. In this context there arises quite naturally a complete set of orthonormal wave packet histories, one of whose key properties is their "explosivity index". In the limit of low index values the wave packets trace out fuzzy world lines. By contrast, in the asymptotic limit of high index values, there are no world lines, not even fuzzy ones. Instead, the wave packet histories are those of entities with non-trivial internal collapse and explosion dynamics. Their details are described by the wave processes in the above-mentioned Mach-Zehnder interferometer. Each one of them is a double slit interference process. These wave processes are applied to elucidate the amplification of waves in an accelerated inhomogeneous dielectric. Also discussed are the properties and relationships among the transition amplitudes of an accelerated finite-time detector.Comment: 38 pages, RevTex, 10 figures, 4 mathematical tutorials. Html version of the figures and of related papers available at http://www.math.ohio-state.edu/~gerlac

Coulomb field of an accelerated charge: physical and mathematical aspects

The Maxwell field equations relative to a uniformly accelerated frame, and the variational principle from which they are obtained, are formulated in terms of the technique of geometrical gauge invariant potentials. They refer to the transverse magnetic (TM) and the transeverse electric (TE) modes. This gauge invariant "2+2" decomposition is used to see how the Coulomb field of a charge, static in an accelerated frame, has properties that suggest features of electromagnetism which are different from those in an inertial frame. In particular, (1) an illustrative calculation shows that the Larmor radiation reaction equals the electrostatic attraction between the accelerated charge and the charge induced on the surface whose history is the event horizon, and (2) a spectral decomposition of the Coulomb potential in the accelerated frame suggests the possibility that the distortive effects of this charge on the Rindler vacuum are akin to those of a charge on a crystal lattice.Comment: 27 pages, PlainTex. Related papers available at http://www.math.ohio-state.edu/~gerlac

Quantum Mechanical Carrier of the Imprints of Gravitation

We exhibit a purely quantum mechanical carrier of the imprints of gravitation by identifying for a relativistic system a property which (i) is independent of its mass and (ii) expresses the Poincare invariance of spacetime in the absence of gravitation. This carrier consists of the phase and amplitude correlations of waves in oppositely accelerating frames. These correlations are expressed as a Klein-Gordon-equation-determined vector field whose components are the ``Planckian power'' and the ``r.m.s. thermal fluctuation'' spectra. The imprints themselves are deviations away from this vector field.Comment: 8 pages, RevTex. Html version of this and related papers on accelerated frames available at http://www.math.ohio-state.edu/~gerlac

Charge carrier interaction with a purely electronic collective mode: Plasmarons and the infrared response of elemental bismuth

We present a detailed optical study of single crystal bismuth using infrared reflectivity and ellipsometry. Colossal changes in the plasmon frequency are observed as a function of temperature due to charge transfer between hole and electron Fermi pockets. In the optical conductivity, an anomalous temperature dependent mid-infrared absorption feature is observed. An extended Drude model analysis reveals that it can be connected to a sharp upturn in the scattering rate, the frequency of which exactly tracks the temperature dependent plasmon frequency. We interpret this absorption and increased scattering as the first direct optical evidence for a charge carrier interaction with a collective mode of purely electronic origin; here electron-plasmon scattering. The observation of a \emph{plasmaron} as such is made possible only by the unique coincidence of various energy scales and exceptional properties of semi-metal bismuth.Comment: 4 pages, 4 figure

ACE-inhibition prevents postischemic coronary leukocyte adhesion and leukocyte-dependent reperfusion injury

Objective: Polymorphonuclear leukocytes (PMN), retained in the microvascular bed, can contribute to postischemic myocardial reperfusion injury. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN dependent reperfusion injury in isolated guinea pig hearts. Methods: Hearts (n=5 per group) were subjected to 15 min of ischemia. Immediately thereafter, a bolus of PMN was injected into the coronary system. External heart work (EHW) and total cardiac nitric oxide release were measured. For microscopic evaluation, hearts received rhodamine 6G labelled PMN after ischemia, were arrested 5 min later and further perfused with FITC dextran (0.1%). Localization of retained PMN was assessed by fluorescence microscopy. Leukocyte activation was studied by FACS analysis of the adhesion molecule CD11b before and after coronary passage of the PMN. The ACE-inhibitor cilazaprilat (Cila, 2 μM) and the NO-synthase inhibitor nitro-L-arginine (NOLAG, 10 μM) were used to modulate nitric oxide formation of the heart. Results: Postischemic EHW recovered to 67±5% (controls) and 64±6% (Cila) of the preischemic value. Addition of PMN severely depressed recovery of EHW (39±2%) and NO release (39±6% of the preischemic value). Simultaneously, ischemia led to a substantial increase in postcapillary PMN adhesion (from 21±5 to 172±27 PMN/mm² surface) and CD11b-expression of the recovered PMN (3-fold). Cila attenuated postischemic PMN adhesion (83±52 PMN/mm²) and activation of PMN, whereas it improved recovery of work performance (64±4%) and NO release (65±4%) in the presence of PMN. Conversely, NOLAG increased PMN adhesion (284±40 PMN/mm²) and myocardial injury. We conclude that ACE-inhibition prevents leukocyte dependent reperfusion injury mainly by inhibition of postcapillary leukocyte adhesion. The effect may be mediated by NO, given the proadhesive effect of NOLAG